Anti-tubercular activity of a natural stilbene and its synthetic derivatives

• Main Authors: Reinheimer, Claudia, Büttner, Dominik, Proschak, Eugen, Bode, Helge B., Kempf, Volkhard A. J., Wichelhaus, Thomas A.
• Format: Article
• Language: English
• Published: German Medical Science GMS Publishing House 2018-02-01
• Series: GMS Infectious Diseases
• Subjects: tuberculosis; drug resistance; new substances; epoxide hydrolases; stilbene
• Online Access: http://www.egms.de/static/en/journals/id/2018-6/id000036.shtml

Objectives: Tuberculosis (TB) and multidrug- and extensively drug-resistant TB in particular are remaining a major global health challenge and efficient new drugs against TB are needed. This study evaluated the anti-tubercular activity of a natural stilbene and its synthetic derivatives against .Methods: Isopropylstilbene and its synthetic derivatives were analyzed for their anti-tubercular activity against ATCC 27294 as well as multidrug- and extensively drug-resistant clinical isolates by using MGIT 960 instrumentation and EpiCenter software equipped with TB eXiST module. Cytotoxic effects of drug candidates were determined by a MTT dye reduction assay using A549 adenocarcinomic human alveolar basal epithelial cells.Results: Growth of ATCC 27294 was suppressed by the natural isopropylstilbene HB64 as well as synthetic derivatives DB56 and DB55 at 25 µg/ml. Growth of clinical isolates MDR and XDR was suppressed by HB64 at 100 µg/ml as well as by synthetic derivatives DB56 and DB55 at 50 µg/ml and 25 µg/ml, respectively. No anti-tubercular activity was demonstrated for synthetic derivatives DB53, EB251, and RB57 at 100 µg/ml. Toxicity in terms of IC values of HB64, DB55 and DB56 were 7.92 µg/ml, 12.15 µg/ml and 16.01 µg/ml, respectively.Conclusions: Synthetical derivatives of stilbene might be effective candidates as anti-tubercular drugs. However, toxicity of these substances as determined by IC values might limit therapeutic success . Further investigations should address lowering the toxicity for parenteral administration by remodeling stilbene derivatives.